The chromosome 1 region has peak markers with of LOD of 3.45 and 3.46 for Alcoholism gender age and constraint as D1S2878 (165403366) D1S196 (167604128). Arbitrary interval of 25 MBp on each side of the peak makers was uploaded.
Authors:
Hill SY, Shen S, Zezza N, Hoffman EK, Perlin M, Allan W
Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.
Authors:
Laura B Ferguson, Lingling Zhang, Daniel Kircher, Shi Wang, R Dayne Mayfield, John C Crabbe, Richard A Morrisett, R Adron Harris, Igor Ponomarev
Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.
Authors:
Laura B Ferguson, Lingling Zhang, Daniel Kircher, Shi Wang, R Dayne Mayfield, John C Crabbe, Richard A Morrisett, R Adron Harris, Igor Ponomarev
Alcohol transcriptome changes in mice microglia p-value
Description:
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.
Authors:
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Data from GEO GSE194368 and analyzed using GEO2R, only top gene shown. Authors identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators and downstream systems may represent viable therapeutic targets to treat the “stress side” of OUD.
Authors:
Stephanie A Carmack, Janaina C M Vendruscolo, M Adrienne McGinn, Jorge Miranda-Barrientos, Vez Repunte-Canonigo, Gabriel D Bosse, Daniele Mercatelli, Federico M Giorgi, Yu Fu, Anthony J Hinrich, Francine M Jodelka, Karen Ling, Robert O Messing, Randall T Peterson, Frank Rigo, Scott Edwards, Pietro P Sanna, Marisela Morales, Michelle L Hastings, George F Koob, Leandro F Vendruscolo
Differential gene expression between CS14 and CS17 - Log2FC
Description:
Human craniofacial tissues were collected from the Joint MRC/Wellcome Trust Human Developmental Biology (HDBR). Donations of tissue to HDBR are made under-informed ethical consent with Research Tissue Bank ethical approval by women undergoing termination of pregnancy. Gene expression profiles were generated from multiple biological replicates of primary craniofacial (CF) tissue from Carnegie Stages (CS) of the embryonic period, CS13, CS14, CS17, CS17, and CS22. Here the differential expression comparison between CS14 and CS17 is shown. Gene expressions values with log to the base 2, FC are presented with P-Adj <0.05. UBERON:0015789, cranial or facial muscle.
Authors:
Tara N Yankee, Sungryong Oh, Emma Wentworth Winchester, Andrea Wilderman, Kelsey Robinson, Tia Gordon, Jill A Rosenfeld, Jennifer VanOudenhove, Daryl A Scott, Elizabeth J Leslie, Justin Cotney
Differential gene expression between CS14 and CS17 - Adj-P value
Description:
Human craniofacial tissues were collected from the Joint MRC/Wellcome Trust Human Developmental Biology (HDBR). Donations of tissue to HDBR are made under-informed ethical consent with Research Tissue Bank ethical approval by women undergoing termination of pregnancy. Gene expression profiles were generated from multiple biological replicates of primary craniofacial (CF) tissue from Carnegie Stages (CS) of the embryonic period, CS13, CS14, CS15, CS17 and CS22. Here the differential expression comparison between CS14 and CS17 is shown. Gene expressions values, Ensembl Gene ids and the corresponding Adjusted P value are presented. UBERON:0015789, cranial or facial muscle.
Authors:
Tara N Yankee, Sungryong Oh, Emma Wentworth Winchester, Andrea Wilderman, Kelsey Robinson, Tia Gordon, Jill A Rosenfeld, Jennifer VanOudenhove, Daryl A Scott, Elizabeth J Leslie, Justin Cotney
Differential gene expression between CS13 and CS22 - Log2FC
Description:
Human craniofacial tissues were collected from the Joint MRC/Wellcome Trust Human Developmental Biology (HDBR). Donations of tissue to HDBR are made under-informed ethical consent with Research Tissue Bank ethical approval by women undergoing termination of pregnancy. Gene expression profiles were generated from multiple biological replicates of primary craniofacial (CF) tissue from Carnegie Stages (CS) of the embryonic period, CS13, CS14, CS17, CS17, and CS22. Here the differential expression comparison between CS13 and CS22 is shown. Gene expressions values with log to the base 2, FC are presented with P-Adj <0.05. UBERON:0015789, cranial or facial muscle.
Authors:
Tara N Yankee, Sungryong Oh, Emma Wentworth Winchester, Andrea Wilderman, Kelsey Robinson, Tia Gordon, Jill A Rosenfeld, Jennifer VanOudenhove, Daryl A Scott, Elizabeth J Leslie, Justin Cotney
Differential gene expression between CS13 and CS22 - Adj-P value
Description:
Human craniofacial tissues were collected from the Joint MRC/Wellcome Trust Human Developmental Biology (HDBR). Donations of tissue to HDBR are made under-informed ethical consent with Research Tissue Bank ethical approval by women undergoing termination of pregnancy. Gene expression profiles were generated from multiple biological replicates of primary craniofacial (CF) tissue from Carnegie Stages (CS) of the embryonic period, CS13, CS14, CS17, CS17 and CS22. Here the differential expression comparison between CS13 and CS22 is shown. Gene expressions values, Ensembl Gene ids and the corresponding Adjusted P value are presented. UBERON:0015789, cranial or facial muscle.
Authors:
Tara N Yankee, Sungryong Oh, Emma Wentworth Winchester, Andrea Wilderman, Kelsey Robinson, Tia Gordon, Jill A Rosenfeld, Jennifer VanOudenhove, Daryl A Scott, Elizabeth J Leslie, Justin Cotney
Differential gene expression between CS14 and CS22 - Adj-P value
Description:
Human craniofacial tissues were collected from the Joint MRC/Wellcome Trust Human Developmental Biology (HDBR). Donations of tissue to HDBR are made under-informed ethical consent with Research Tissue Bank ethical approval by women undergoing termination of pregnancy. Gene expression profiles were generated from multiple biological replicates of primary craniofacial (CF) tissue from Carnegie Stages (CS) of the embryonic period, CS13, CS14, CS17, CS17 and CS22. Here the differential expression comparison between CS14 and CS22 is shown. Gene expressions values, Ensembl Gene ids and the corresponding Adjusted P value are presented. UBERON:0015789, cranial or facial muscle.
Authors:
Tara N Yankee, Sungryong Oh, Emma Wentworth Winchester, Andrea Wilderman, Kelsey Robinson, Tia Gordon, Jill A Rosenfeld, Jennifer VanOudenhove, Daryl A Scott, Elizabeth J Leslie, Justin Cotney
Whole Brain Gene Expression Correlates for AMDIST135 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The AMDIST135 measures Morphine distance (cm) travelled minutes 120-135 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for AMDIST165 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The AMDIST165 measures Morphine distance (cm) travelled minutes 150-165 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for AMDIST180 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMDIST180 measures Morphine distance (cm) travelled minutes 165-180 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for LM_SUPPRESSION measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The LM_SUPPRESSION measures Cue Conditioning - Activity suppression after 3rd tone/shock pairing under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for LM_SUPPRESSION measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The LM_SUPPRESSION measures Cue Conditioning - Activity suppression after 3rd tone/shock pairing under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Whole Brain Gene Expression Correlates for AMCNT120 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The AMCNT120 measures Morphine photocell counts minutes 105-120 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for AMCNT135 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The AMCNT135 measures Morphine photocell counts minutes 120-135 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for AMCNT165 measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT165 measures Morphine photocell counts minutes 150-165 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for AMCNT165 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT165 measures Morphine photocell counts minutes 150-165 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for AMCNT180 measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT180 measures Morphine photocell counts minutes 165-180 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for AMCNT180 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT180 measures Morphine photocell counts minutes 165-180 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Whole Brain Gene Expression Correlates for AMDIST120 measured in BXD RI Females & Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The AMDIST120 measures Morphine distance (cm) travelled minutes 105-120 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Hippocampus Gene Expression Correlates for ENTRIES_CLOSED measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ENTRIES_CLOSED measures Number of entries into closed arms of plus maze under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
Hippocampus Gene Expression Correlates for SPD_TIMEDOWEL30SEC measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The SPD_TIMEDOWEL30SEC measures Dowel Test - Time 30 Sec under the domain Porsolt. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
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